Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present series of studies of CSF monoamine metabolites support the hypothesis of a role for serotonin in depressive illness, insofar that depressed patients have slightly lower CSF 5-HIAA concentrations than normal controls. Apparently a normal association between CSF 5-HIAA and platelet MAO activity is disrupted in depression. The importance of serotonin does not, however, appear to be confined to depressive illness. There is a strong association between a low CSF 5-HIAA and a tendency to suicidal behaviour, also outside the setting of depression. The nature of this relationship is unclear, but it is suggested that certain personality features may form a mediating link. A connection between a low serotonin turnover and a weakened control of aggressive or hostile impulses is one possibility.
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PMID:Studies of CSF 5-HIAA in depression and suicidal behaviour. 617 23

The antidepressant and biochemical effects of femoxetine, a selective serotonin uptake inhibitor, and desipramine, a selective nor-adrenaline uptake inhibitor, have been compared in a double-blind study in 42 outpatients with depressive illness. The patients were allocated at random to treatment with either 600 mg femoxetine or 150 mg desipramine daily for 6 weeks. The total depression score showed a significant decrease in both groups, indicating an overall improvement in depressive symptoms. The patients treated with femoxetine reported significantly less severe anticholinergic effects during the whole treatment period than the desipramine patients. Both drugs, decreased the level of 5-HIAA in CSF, whereas no consistent changes were found in the MHPG and HVA levels. The pretreatment level of the metabolites had no predictive value for the outcome of the treatment with either drug. No significant correlation was found between therapeutic effect and the plasma concentration of the active compounds.
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PMID:Antidepressant effect of femoxetine and desipramine and relationship to the concentration of amine metabolites in cerebrospinal fluid. A double-blind evaluation. 618 53

Untreated adult coeliac patients have previously been shown to have a high frequency of depressive symptoms as reported in a personality inventory (the MMPI). In the present study we determined the concentrations of three major monoamine metabolites in samples of lumbar cerebrospinal fluid of ten consecutive adults with newly detected coeliac disease. They showed significant reduction in levels of 5-HIAA (70.3 +/- 25.4 pmol/ml). HVA (128.2 +/- 58.3 pmol/ml), and MOPEG (27.7 +/- 7.4 pmol/ml), indicating reduced central metabolism in all three monoamine pathways. The concentrations, in particular that of MOPEG, were inversely correlated with depressive symptoms reported on the MMPI scale 2 ('depression'), which conforms with current concepts on the pathogenesis of depression.
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PMID:Psychic disturbances in adult coeliac disease. III. Reduced central monoamine metabolism and signs of depression. 618 5

Adults with intestinal malabsorption due to celiac disease show reduced central serotonin metabolism, probably induced by a lack of essential dietary factors. Investigating a role proposed for vitamin B6 deficiency, a regular finding in untreated celiacs, the present study yields no support for the hypothesis that direct inhibition at the decarboxylation step by vitamin B6 deficiency accounts for low central serotonin turnover in adult celiacs: 11 untreated patients showing reduced 5-HIAA in the cerebrospinal fluid (71+/- 26.8 pmol/ml) had a significantly higher concentration of the metabolically active B6 vitamer pyridoxal 5'-phosphate in lumbar cerebrospinal fluid (0.06 +/- 0.34 ng/ml) than controls (0.24 +/- 0.07 ng/ml) (p less than 0.01). Cerebrospinal fluid tryptophan, precursor of serotonin, was normal (2035 %/- 649 pmol/ml). Raised pyridoxal 5'-phosphate in the cerebrospinal fluid in untreated celiac disease is an unexpected finding. Possibly it is secondary to the diminished central monamine metabolism in these patients, but further studies are needed bearing in mind that mental depression is a major cause for disability in adult celiac disease.
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PMID:High level of pyridoxal 5'-phosphate in the cerebrospinal fluid of adult celiac patients. 618 88

As part of the National Institute of Mental Health Clinical Research Branch Collaborative Program on the Psychobiology of Depression, the authors compared concentrations of CSF monoamine metabolites (the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol [MHPG], the dopamine metabolite homovanillic acid [HVA], and the serotonin metabolite 5-hydroxyindoleacetic acid [5-HIAA]) from 14 hospitalized manic patients with concentrations from 62 healthy comparison subjects. The manic patients had significantly higher levels of MHPG. Levels of 5-HIAA and HVA did not differ between the manic patients and the comparison male subjects, but they were elevated in the female manic patients. MHPG was the only metabolite that correlated significantly with mania symptom ratings. These data are consistent with findings that have shown abnormal, perhaps excessive, central noradrenergic activity in patients with mania, but not with those suggesting deficits in serotoninergic function.
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PMID:CSF monoamine metabolites in mania. 618 81

5-Hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured in the spinal fluid of 45 women hospitalized in a psychiatric department for major depression (14 cases), schizophrenia (18 cases) and alcohol dependence (13 cases). Dexamethasone suppression tests were performed following CSF examinations in all patients, and TRH stimulation tests were also made in six subjects. All biological examinations were carried out in a drug-free state. The Marke-Nyman Temperament scale was administered to all patients as soon as severe psychotic disturbances subsided and sufficient cooperation was achieved, but no later than 10 days following biological examinations. The MNT was repeated after recovery to check reliability of the test results during an episode of a psychiatric disorder. CSF amine metabolite concentrations did not differ significantly in the three patient groups; postdexamethasone average cortisol levels were above the critical level (5 micrograms/dl) in each group, the highest values being found in major depression. One of the three MNT factors was inhomogeneous among diagnostic groups (validity: low in depression and alcoholism), but the other two also differed from a healthy control population. Correlation structure between biological and psychological variables was homogeneous throughout the diagnoses and a significant inverse correlation was found only between CSF 5-HIAA and the validity factor of MNT. Maximal TSH response to TRH stimulation correlated with both solidity and stability in the MNT scale. Since MNT results proved to be stable even during an illness episode, a possible link is suggested between personality traits and central serotonin metabolism.
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PMID:Relationship between cerebrospinal fluid amine metabolites, neuroendocrine findings and personality dimensions (Marke-Nyman scale factors) in psychiatric patients. 619 Mar 56

5-Hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured in the lumbar cerebrospinal fluid of 57 drug-free female patients with DSM-III diagnoses of major unipolar or bipolar depression (n = 14), schizophrenic disorder (n = 18), alcohol dependence (n = 13) and a group of other disorders (n = 12). Following lumbar punctures all patients received a dexamethasone suppression test. Fourteen patients had attempted suicide immediately before admission, 4 of them by violent methods. Severity of depression, independent of the diagnosis, was assessed in every patient on the 24-item Hamilton scale. No significant differences in means and variances of amine metabolite or postdexamethasone plasma cortisol concentrations were found among the diagnostic subgroups. Suicidal patients, and in particular those who used violent methods, tended to have lower 5-HIAA, but not HVA, in their CSF; they also more often had non-suppression of cortisol after dexamethasone. Since correlation matrices in the diagnostic subgroups were homogeneous, we calculated partial correlations for the total group: here suicide attempts but not depression, seemed to be significantly correlated with CSF 5-HIAA. Thyrotropin stimulation tests were administered to 6 patients: maximal TSH responses showed a borderline significant correlation with CSF 5-HIAA, and a significant correlation with severity of depression. Neither suicide nor postdexamethasone cortisol levels showed any relation to maximal TSH changes.
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PMID:Amine metabolites and neuroendocrine responses related to depression and suicide. 619 56

5-Hydroxyindoleacetic acid (5HIAA), homovanillic acid (HVA), cortisol (CS), tryptophan (TRY), and calcium (Ca) concentrations were measured in the spinal fluid of 85 female psychiatric inpatients in a drug-free state; 32 women suffered from major depression, another 32 had schizophrenic (or schizophreniform) disorder, and 21 had alcohol dependence as defined by DSM-III criteria. A dexamethasone suppression test (DST) was carried out following lumbar punctures in all patients. Biochemical results were analyzed by two-way analysis of variance to test the effect of diagnosis and dexamethasone nonsuppression. CS concentration proved to be significantly higher in dexamethasone nonsuppressors, independent of the diagnosis. HVA was lower in nonsuppressors, particularly in alcohol-dependent patients; 5HIAA showed a tendency to be higher in nonsuppressor depressed patients. TRY was again higher in nonsuppressors, significant only in schizophrenic patients. Ca concentration was higher in depression and lower in alcohol dependence, and within the depression group it was higher in normal DST patients. The results indicate that the primarily biological dysfunction, i.e., the limbic-hypothalamic disinhibition reflected in the DST, may be more closely related to spinal fluid biochemistry than clinical syndromes.
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PMID:Cerebrospinal fluid biochemical examinations: do they reflect clinical or biological differences? 619 59

Relationships between pretreatment neurotransmitter metabolite levels and response to imipramine and amitriptyline were studied in 104 depressed patients. Normal values for urinary norepinephrine and low values for urinary MHPG were associated with greater incidence of drug response in bipolar, but not unipolar, patients. For unipolar, but not bipolar, patients low CSF 5-HIAA and high urinary metanephrine values were associated with a greater incidence of drug response. These data indicate that the pretreatment functional state of catecholamine and serotonin systems is associated with type of response to drug treatment. The authors present hypotheses about the association of alterations in serotonin and norepinephrine systems and definable subtypes of depression.
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PMID:Pretreatment neurotransmitter metabolite levels and response to tricyclic antidepressant drugs. 620 36

The effect of the learned helplessness paradigm, a model of depression, on biogenic amines in eight brain regions, and on the serum levels of luteinizing hormone, corticosterone, and testosterone in male rats was determined. Rats which were exposed to uncontrollable and unpredictable shocks (HY-rats) had hormone levels similar to those in appropriate control animals. However, HY-rats had higher levels of 5-HIAA in the pons/medulla oblongata and lower levels of 5-HT in the cortex than rats which could escape the shocks (HE-rats). Furthermore, striatal levels of NE were higher in HY-rats when compared to HE-rats and non-shocked controls (HC-rats). Shock treatment per se resulted in lower NE levels in the hippocampus. These data implicate the serotonergic and noradrenergic systems as possible mediators of the learned helplessness phenomenon, but do not support the view that this behavior is associated with impaired pituitary-gonadal function.
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PMID:Learned helplessness: effects on brain monoamines and the pituitary-gonadal axis. 654 25


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